Bacterial luciferase is a heterodimer (Alpha Beta) with a single active center residing primarily if not exclusively on the Alpha subunit. The enzyme is a flavin hydroxylase which catalyzes the conversion of a long-chain saturated aldehyde to the carboxylic acid via a 4a-peroxydihydroflavin intermediate. The reaction leaves the flavin in an electronically excited state which returns to ground state by emission of a photon of blue-green light. Bacterial luciferase is an excellent model for study of not only the flavin monooxygenase system, but also the processes of enzyme inactivation and turnover, and the processes of molecular aging. The luciferase in a culture of the luminous marine bacterium Vibrio harveyi is rapidly inactivated as the culture enters late log and early stationary phase of growth. We have shown that the processes of inactivation and turnover are discrete and experimentally separable. We have isolated two classes of mutants of V. harveyi in which the luciferase is not inactivated in stationary phase cells. In the wild-type cells, the specific activity of the luciferase enzyme decreases as the cells enter stationary phase in a fashion very similar to the decrease in specific activity reported for some enzymes in aging organisms. However, in one class of mutants that does not inactivate luciferase during stationary phase of growth, the aldehyde-deficient mutants, the specific activity of the luciferase does not decline. Using a combination of the classical techniques of protein chemistry and enzymology and the immunochemical blotting techniques, we have shown that the inactivation of luciferase is associated with a decrease in solubility of the protein. It appears that the inactive, aggregated luciferase is the target for proteolysis that results in turnover. Our proposal is to deterine the biochemical alterations in the luciferase which render it inactive. These studies should contribute to a fundamental understanding of the physico-chemical properties of proteins that dictate their specific lifetimes in the living cells.